Lecture 15 Pain Syndromes and Analgesics Flashcards
Pain
A normal unpleasant physical sensation associated with tissue damage or dysfunction
What are the two major types of pain?
Physiological (nociceptive) and chronic (intractable, neuropathic)
Congentical absence of pain…
Rare genetic defect in which a person has normal skin sensation but is unable to perceive pain from birth; compound fractures, loss of body parts can go unnoticed
Nociception
“noxious perception” the perception of pain
Nociceptor
Receptor for stimuli (chemical, mechanical, thermal) that result in pain perception; located on free nerve endings in skin, muscle, organs
Analgesia
absence of pain
Anesthesia
Absence of all sensory perception
Anesthetic
A substance that reduces perception of numerous senses (touch, pain, temperature, pressure)
Analgesic
A substance that diminishes the perception of pain
Names some pain syndromes
Lower back pain Headache /migraine Cancer-related Fibromyalgia Sciatica Diabetic neuropathy Shingles Phantom limb pain burn pain Arthritis Trigeminal neuroalgia
A(delta) fibers
Myelinated fibers (20 m/sec) for quick, sharp pain
C fibers
Unmyelinated fibers (2 m/sec) for dull, slow pain
Aβ fibers
normal mechanical stimuli signals
PN
Projection neurons (ascends up to brain); receive pain signals at the dorsal root of the spinal cord
What are the nerve fibers that conduct pain signals?
A(delta), C fibers, Projection neurons
What results from tissue damage?
Tissue damage causes the release of various chemicals that activate pain fibers, such as histamine, bradykinin (BK), and prostaglandins.
TRP receptors
Transient receptor potential (TRP) receptors, including vanilloid receptors (i.e., VR1) are thermosensitive and chemosensitive receptors on free nerve endings.
What activates TRP receptors
Activated by heat, changes in pH, capsaicin (chili peppers), wasabi, etc
How does pain arise from demyelination?
Accumulation of voltage-sensitive sodium channels (VSSCs) in demyelinated areas of sensory neurons increases ectopic (“out of place”, spontaneous) activity, and hypersensitivity to normal sensations
How does pain occur after severing a nerve?
Neuroma – misguided bundle of newly sprouted nerve fibers following nerve cut
Accumulation of VSSCs in neuromas increases ectopic activity, and hypersensitivity to normal sensations
Neuroma
Misguided bundle of newly sprouted nerve fibers following nerve cut.
Where does all sensory information enter in the spinal cord?
The dorsal horn of the spinal cord.
Where is the reduction of emotional components of pain managed?
The amygdala
Where does the inhibition of pain signals occur
The thalamus
Spinal and supraspinal analgesia
spinal analgesia is when drugs act at the spine
supraspinal is when drugs act at the brain
What are the pain neurotransmitters in the spinal cord?
opioid (µ, delta, kappa), 5-HT, and NE
What modulates descending pain pathways?
NE (from locus coeruleus) and 5-HT (from raphe nuclei) modulate pain in the spinal cord
SSRI, SNRI, NRIs can thus alleviate chronic pain in some patients
Name some local anesthetics?
Novocaine, lidocaine, cocaine
How do local anesthetics work?
- block VSSCs on sensory neurons
- loss of action potentials results in reduced sensation of pain, touch, pressure, temperature (numbness)
- must be given locally (i.e., topical subcutaneous injection, epidural)
COX
Cyclooxygenase (COX) - enzyme that produces prostaglandins which are released from cells after tissue injury; prostaglandins activate pain pathways
NSAID
- Non-steroidal anti-inflammatory drugs (NSAIDs) are COX inhibitors
- aspirin, ibuprofen, naproxen, acetaminophen (Tylenol), prescription COX inhibitors (Vioxx, Celebrex)
Synthetic steroids
(i.e. hydrocortisone, prednisone) – reduce peripheral inflammation (not via COX inhibition), but long term use is harmful to immune system
Anticonvulsants can be used for what type of pain?
Neuropathic pain
What are the mechanisms of anticonvulsants for pain?
- Inhibition of VSSCs and voltage-sensitive Ca+ channels
- Inhibition of GABA reuptake/metabolism
Where do opiates act on?
Act primarily on mu (m) opioid receptors located on primary afferent terminals in dorsal horn of spinal cord.
What normally activates the mu opioid receptors?
normally activated by endorphins and enkephalins
inhibit transmission of pain signals to brain
What are some side effects of opioids?
side effects include sedation, respiratory depression, constipation, tolerance, dependence, & addiction.
What are endocannabinoids generated from?
Arachidonic acid (a fatty acid found in the cell membrane) after stimulation of certain neurotransmitter receptors.
Cannabinoids are what type of messenger?
Act as retrograde messengers to inhibit neurotransmitter release.
THC is an agonist at what receptors?
THC is an agonist at cannabinoid (CB1) receptors
What are 3 synthetic THC and cannabinoids?
Sativex, Marinol, Cesamet
Why can’t cannabinoids be stored in vesicles?
They are highly lipid soluble (therefore cannot be stored in vesicles)
What are the 4 phases of a migraine?
- Prodrome
- Aura
- Pain phase
- Postdrome
Prodrome
Symptoms such as altered mood, fatigue, yawning, excessive sleepiness, craving for certain food, stiff muscles, hot ears, GI problems, etc. appear hours to days before migraine
Aura
Disturbance of vision just before headache
Pain phase
Headache on one side of head with nausea, photophobia
Postdrome
Exhaustion, irritability, depression
What are common migraine triggers?
- Estrogen and progesterone
- Alcohol, chocolate, etc.
- Stress, physical activity
- Sight, smells
- Certain medications
What are four types of headaches?
Sinus, cluster, tension, migraine
Trepenation
Medieval treatment
(drilling hole in skull), hot iron to the head, blood letting.
What was the first effective medication for migraines?
Ergotamine which constricts blood vessels
Triptans
Sumatriptan (Imitrex), zolmitriptan (Zomig), naratriptan, rizatriptan, eletriptan, almotripan, etc.
What are the mechanisms of triptans?
Cause vasoconstriction via stimulation of 5-HT1B serotonin receptors on blood vessel walls, also reduce inflammation of vessels by stimulation of 5-HT1D serotonin receptors in brainstem.
Phantom limb pain
-Tingling, itching, burning, aching, stabbing sensations that appear to emanate from body parts post amputation
What was the historical theory for phantom limb pain?
Historically, the dominant theory for cause of phantom limb pain was the presence of neuromas that generated nonsense sensations
What are todays theory of phantom limb pain?
- maladaptive reorganization of the primary sensory cortex
- conflict between signals received from the amputated limb (proprioception) and visual information
- vivid limb position memories that emerge after amputation
What are common treatments for phantom limb pain?
Common treatments are antidepressants, spinal cord stimulation, vibration therapy, acupuncture, hypnosis, biofeedback, and mirror therapy.
Generally not relieved by opiate analgesics.
